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Original Article Malta Medical School Gazette Volume 03 Issue 03 2019 Abstract Aim: The aim of this audit was to assess adherence to local guideline in the management of Diabetic Ketoacidosis (DKA). Method: Patients admitted with DKA between April 2013 and March 2015 were identified and data was retrospectively collected from patients’ confidential files and Isoft ® . Data collected included initial parameters recorded and biochemical investigations taken (initial and subsequent assessment of pH, HCO 3- , blood glucose, potassium levels and urinary ketones), insulin regime started and intravenous fluid administered. Results: During the established time period 40 cases of DKA were identified in 18 patients. Median age was 33 years with a female preponderance of 60%. Six patients had newly diagnosed diabetes mellitus while 8 patients had more than one admission of DKA. All cases had capillary blood glucose monitoring (BGM) and/or venous random blood (plasma) glucose (RBG) checked and pH and HCO 3- recorded on admission. 0.9% sodium chloride was the intravenous fluid started in all cases (as recommended by the guideline) and a median of 6.75L was prescribed during the first 24 hours. The median time spent on intravenous insulin infusion was 42.7 hours while the median time to pH >7.30, HCO 3- >15mmol/L and negligible urinary ketones were 6.88, 12.83 and 34.5 hours respectively. Subcutaneous insulin was started at a median time of 48.21 hours from initiation of DKA protocol. Conclusion: This audit showed good adherence to local guideline. The great discrepancy between the time to pH >7.3 and the time to negligible urinary ketones highlights the need to introduce tools to measure systemic ketone production in the management of DKA with an update in the current local clinical practice guideline. Presentation and management of diabetic ketoacidosis in adults in Malta Miriam Giordano Imbroll, Alison Psaila, Alexia-Giovanna Abela, Mark Gruppetta, Sandro Vella, Josanne Vassallo, Mario J. Cachia, Stephen Fava Miriam Giordano Imbroll MD MRCP * Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Department of Medicine, Mater Dei Hospital, Msida, Malta. [email protected] Alison Psaila MD MRCP Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Department of Medicine, Mater Dei Hospital, Msida, Malta. Alexia-Giovanna Abela MD MRCP Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Department of Medicine, Mater Dei Hospital, Msida, Malta. Mark Gruppetta MD PhD Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Department of Medicine, Mater Dei Hospital, Msida, Malta. Sandro Vella MD (Melit) MD (Dund) Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Department of Medicine, Mater Dei Hospital, Msida, Malta. Josanne Vassallo MD PhD Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Department of Medicine, Mater Dei Hospital, Msida, Malta. Mario J. Cachia MD FRCP Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Department of Medicine, Mater Dei Hospital, Msida, Malta. Stephen Fava MD PhD Department of Medicine, Faculty of Medicine and Surgery, University of Malta, Department of Medicine, Mater Dei Hospital, Msida, Malta. 3

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  • Editorial OrgOdRe

    Original Article

    Malta Medical School Gazette Volume 03 Issue 03 2019

    Abstract

    Aim: The aim of this audit was to assess

    adherence to local guideline in the management of

    Diabetic Ketoacidosis (DKA).

    Method: Patients admitted with DKA between

    April 2013 and March 2015 were identified and

    data was retrospectively collected from patients’

    confidential files and Isoft®. Data collected

    included initial parameters recorded and

    biochemical investigations taken (initial and

    subsequent assessment of pH, HCO3-, blood glucose,

    potassium levels and urinary ketones), insulin

    regime started and intravenous fluid administered.

    Results: During the established time period 40

    cases of DKA were identified in 18 patients.

    Median age was 33 years with a female

    preponderance of 60%. Six patients had newly

    diagnosed diabetes mellitus while 8 patients had

    more than one admission of DKA. All cases had

    capillary blood glucose monitoring (BGM) and/or

    venous random blood (plasma) glucose (RBG)

    checked and pH and HCO3- recorded on admission.

    0.9% sodium chloride was the intravenous fluid

    started in all cases (as recommended by the

    guideline) and a median of 6.75L was prescribed

    during the first 24 hours. The median time spent on

    intravenous insulin infusion was 42.7 hours while

    the median time to pH >7.30, HCO3- >15mmol/L

    and negligible urinary ketones were 6.88, 12.83 and

    34.5 hours respectively. Subcutaneous insulin was

    started at a median time of 48.21 hours from

    initiation of DKA protocol.

    Conclusion: This audit showed good adherence

    to local guideline. The great discrepancy between

    the time to pH >7.3 and the time to negligible

    urinary ketones highlights the need to introduce

    tools to measure systemic ketone production in the

    management of DKA with an update in the current

    local clinical practice guideline.

    Presentation and management of diabetic

    ketoacidosis in adults in Malta

    Miriam Giordano Imbroll, Alison Psaila, Alexia-Giovanna Abela,

    Mark Gruppetta, Sandro Vella, Josanne Vassallo, Mario J. Cachia,

    Stephen Fava Miriam Giordano Imbroll MD MRCP *

    Department of Medicine,

    Faculty of Medicine and Surgery, University of Malta,

    Department of Medicine,

    Mater Dei Hospital, Msida, Malta.

    [email protected]

    Alison Psaila MD MRCP

    Department of Medicine,

    Faculty of Medicine and Surgery, University of Malta,

    Department of Medicine, Mater Dei Hospital, Msida, Malta.

    Alexia-Giovanna Abela MD MRCP

    Department of Medicine,

    Faculty of Medicine and Surgery, University of Malta,

    Department of Medicine,

    Mater Dei Hospital, Msida, Malta.

    Mark Gruppetta MD PhD

    Department of Medicine,

    Faculty of Medicine and Surgery, University of Malta,

    Department of Medicine, Mater Dei Hospital, Msida, Malta.

    Sandro Vella MD (Melit) MD (Dund)

    Department of Medicine,

    Faculty of Medicine and Surgery, University of Malta,

    Department of Medicine,

    Mater Dei Hospital, Msida, Malta.

    Josanne Vassallo MD PhD

    Department of Medicine,

    Faculty of Medicine and Surgery, University of Malta, Department of Medicine,

    Mater Dei Hospital, Msida, Malta.

    Mario J. Cachia MD FRCP

    Department of Medicine,

    Faculty of Medicine and Surgery, University of Malta,

    Department of Medicine,

    Mater Dei Hospital, Msida, Malta.

    Stephen Fava MD PhD

    Department of Medicine,

    Faculty of Medicine and Surgery, University of Malta, Department of Medicine,

    Mater Dei Hospital, Msida, Malta.

    3

  • Editorial OrgOdRe

    Original Article

    Malta Medical School Gazette Volume 03 Issue 03 2019

    Keywords

    Diabetes type 1, Diabetic Ketoacidosis,

    Complications, Mater Dei Hospital

    Introduction

    Diabetic ketoacidosis (DKA) is defined by the

    biochemical triad of ketone production,

    hyperglycaemia and acidaemia. Although not

    common, mortality from DKA is approximately

    2%,1 however, each death is potentially avoidable.

    Increasing patient and healthcare professional

    education and awareness of DKA and its

    management, has led to a decline in mortality over

    recent years.

    The current audit aimed to assess the

    management of patients with DKA and compare

    these practices with the local DKA guideline issued

    in 2007.3 Changes in current practice that could

    improve patient care and shorten hospital stay will

    be identified and instituted.

    Methods

    All adult patients (>16years of age) admitted

    with DKA to Mater Dei Hospital (MDH) over a two

    year period, between April 2013 and March 2015

    were identified. These were identified from the

    Accident and Emergency (A&E) admission book

    and the Electronic Case Summary system. Patients’

    confidential files and Isoft® investigations were

    analysed in detail and predefined data sets obtained,

    in line with Data Protection Act. Only patients with

    parameters fulfilling the biochemical triad of DKA:

    1) blood glucose > 11.0mmol/L or known to have

    diabetes mellitus, 2) metabolic acidosis with HCO3-

    2+ on standard urine sticks,

    were included in the study.4 The identified patients

    had their DKA management analysed in detail and

    compared to the current DKA guideline3 available

    at MDH. All data was recorded on Microsoft Excel

    spreadsheet and analysis of data was then

    performed using IBM SPSS® version 22.

    Kolmogorov–Smirnov test was carried out to

    determine the normal distribution of the data and

    then either T-Test / ANOVA (for parametric data)

    or Mann-Whitney U / Kruskal–Wallis or χ2 (for

    non-parametric data) tests were used as appropriate.

    Correlation analyses were carried out using

    Spearman correlation.

    Results

    1. Demographics Using the criteria above to define DKA, 40

    cases (n = 40) were identified in a total of 18

    different patients, during the study period. In the

    cases studied the median age was 33 years (IQR 24

    – 52.25) with a female predominance of 60%. Six

    patients (33.3%) had newly diagnosed diabetes. 8

    patients (44.4%) had more than one admission with

    DKA during the studied period.

    2. Initial Assessment and investigations Vital parameters (temperature (T), systolic

    blood pressure (SBP), Glasgow coma scale (GCS),

    oxygen saturation (SO2%) and pulse (P)) at

    presentation, as documented in casualty were

    analysed (Table 1).

    On admission all patients had recorded bedside

    capillary blood glucose monitoring (BGM). BGM

    was recorded as ‘HI’ in 7 cases, while the median

    reading in 32 cases was 25.7mmol/L (IQR 23.48 –

    30). Venous random blood (plasma) glucose (RBG)

    was documented in 29 cases and the median was

    33.6mmol/L (IQR 25.2 – 37.4). All 40 cases had pH

    and HCO3- levels checked, in 33 cases by an arterial

    blood gas (ABG) and 7 cases by a venous blood gas

    (VBG) analysis. The median pH of the study

    population at presentation was 7.18 (IQR 7.11 –

    7.24) while the median value for HCO3- was 7.4

    (IQR 5.4 – 11.45). A urine sample confirming

    ketonuria was obtained in 22 cases in the A&E

    Department.

    Additional investigations recommended by the

    current DKA guideline3 include a complete blood

    count (CBC), renal profile (U&E, Cr), arterial blood

    gases (ABG), urinalysis, pregnancy test in female

    patients, ECG and chest x-ray (CXR). An amylase

    level is recommended in patients with abdominal

    pain. The frequency and results of these tests in

    concordance to the local guideline is illustrated in

    Table 1.

    All cases were admitted to Mater Dei Hospital,

    with 4 cases requiring admission to intensive

    therapy unit (ITU).

    4

  • Editorial OrgOdRe

    Original Article

    Malta Medical School Gazette Volume 03 Issue 03 2019

    Table 1: Parameters and investigations with respective median results measured at admission

    Table 2: Frequency of ABG/VBG testing with median results for pH and HCO3-

    Time of

    ABG/VBG (hrs from start

    of protocol)

    Frequency

    (n)

    Percentage

    (%) Median pH

    (mmHg) (IQR) Median HCO3- (mmol/L) (IQR)

    0 40 100 7.19 (7.11 - 7.25) 7.4 (5.4 - 11.45)

    2 33 82.5 7.22 (7.18 - 7.27) 8.7 (5.4 - 13.2)

    4 29 72.5 7.27 (7.22 - 7.31) 8.6 (7.2 - 13.7)

    8 35 87.5 7.33 (7.28 - 7.37) 14 (12.2 - 16.6)

    12 33 82.5 7.36 (7.34 - 7.40) 16.6 (15.4 - 19.0)

    24 14 35 7.42 (7.36 - 7.43) 18 (16.6 - 20.5)

    Parameters and

    investigations on

    admission

    Frequency (n) Median (Interquartile Range)

    Temperature (℃) 38 36.4 (36 - 36.8)

    GCS 40 15

    Oxygen saturation (%) 37 99 (98 - 99)

    SBP (mmHg) 39 121 (107 - 134.5)

    Pulse rate (/min) 39 103 (93 - 120)

    White cell count (x109/L) 40 13.55 (8.78 - 19.98)

    Creatinine (μmol/L) 40 104 ( 94.75 - 120.5)

    eGFR (mls/min/1.73m2) 40 60.5 (48.25 - 71.25)

    Amylase (U/l) 24 39 (35 - 76.75)

    ECG 39 n/a

    CXR 33 n/a

    5

  • Editorial OrgOdRe

    Original Article

    Malta Medical School Gazette Volume 03 Issue 03 2019

    Table 3: Frequency of K level checked and median level at time interval 0, 2, 4, 8, 12 and 24 hours from start

    of DKA protocol

    3. ABGs/VBGs According to current local DKA guideline, pH

    and HCO3- should be measured at 2, 4, 8, 12 hours

    after starting the protocol or until normalisation of

    metabolic acidosis. All patients had ABGs/VBGs

    repeated until pH and HCO3- levels had normalised

    but not necessarily within the stipulated time

    intervals (see table 2).

    4. Ketones The current DKA guideline recommends

    measuring urinary ketones every 4 hours until

    clearance is achieved. Ketones were checked

    regularly in 38 cases (95%) during the first 24

    hours, while 29 patients still required urinary ketone

    testing for more than 24 hours after starting DKA

    treatment protocol. In the initial 24 hours after

    starting treatment the median number of times

    urinalysis was performed was 4 times (IQR 3 –

    5.75) with a median of 2 times (IQR 1 – 3) at 24 –

    48 hours.

    5. BGM Hourly BGM checks are recommended in the

    current local DKA guideline, for patients on

    intravenous insulin infusion. The median number of

    BGM checked was 17.5 times (IQR 9.75 – 22.25)

    during the first 24 hours and 4 times (IQR 3 – 5.75)

    at 24 – 48 hours from admission.

    6. Insulin administration All cases studied were treated with a variable-

    rate insulin infusion (VRIII) of short-acting insulin

    (Actrapid®). Long-acting basal insulin together with

    intravenous Actrapid® was co-administered in 4

    cases (10%). The median time spent on Actrapid®

    infusion was 42.7 hours (IQR 27.9 – 65.75). During

    this period of time the median number of units of

    insulin required was 89Units (IQR 65 – 114) in the

    first 24 hours of protocol and 66Units (IQR 54.5 –

    83) at 24 – 48 hours. Total insulin dose in the first

    24 hours was positively correlated with initial RBG

    (ρ=0.381, P= 0.024). In 7 cases (18%), a further

    increase in insulin was required to reach target

    BGM.

    7. Intravenous fluids All patients were started on 0.9% of sodium

    chloride in concordance with the local guideline.

    The patients received a median of 6.75L (IQR 6.11

    – 7.45L) during the first 24 hours. 10 cases (25%)

    did not require intravenous fluid for more than 24

    hours, while 30 cases (75%) received a median of

    2L (IQR 0.5 – 2.72L) at 24 – 48 hours from starting

    DKA protocol.

    Intravenous fluids are to be changed to 5%

    dextrose in normal saline if BGM is less than

    11mmol/L and to 10% dextrose if BGM is less than

    5mmol/L in the current local DKA guideline.

    Intravenous fluids were correctly changed in 36

    cases when BGM fell below 11mmol/L. In 10 cases

    BGM fell less than 5mmol/L during the initial 24

    hours and 9 of these cases had the intravenous fluid

    correctly changed to 10% dextrose.

    Time of K (hrs from start of protocol)

    Frequency of K level checked n

    (%) Median K level (mmol/L)

    (IQR)

    0 40 (100) 4.7 (4.2 – 5.1)

    2 31 (78) 4 (3.4 - 4.4)

    4 29 (73) 4.3 (3.9 - 4.5)

    8 35 (88) 3.8 (3.5 - 4.4)

    12 32 (80) 3.9 (3.5 - 4.1)

    24 22 (55) 3.7 (3.2 - 4.1)

    6

  • Editorial OrgOdRe

    Original Article

    Malta Medical School Gazette Volume 03 Issue 03 2019

    Table 4: Correlation between different parameters in DKA management

    Results in bold are statically significant (P7.3

    Time

    Period till HCO3-

    >15

    Time Period till

    urine Ketones -

    ve

    Hours on Actrapid

    pump

    HCO3- ρ 0.560 -0.323 -0.500 -0.386 0.070 -0.630 0.487 -0.296 -0.396 -0.0630 -0.444 -0.497

    P

  • Editorial OrgOdRe

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    Malta Medical School Gazette Volume 03 Issue 03 2019

    8. Potassium supplementation The current guideline suggests checking

    potassium (K) levels at 2, 4, 8, and 12 hours and to

    add supplemental potassium chloride into the

    intravenous fluid solution according to results.

    Table 3 shows frequency and results of K level at

    the time intervals recommended. Correlation

    analysis showed K levels at presentation to be

    positively correlated with increasing age and RBG

    (ρ=0.314, P=0.049 and ρ=0.406, P=0.014

    respectively). (Table 4)

    9. Additional management In 7 cases insulin was infused via pump at a

    higher rate than recommended by protocol while in

    2 cases the intravenous fluids prescribed after

    admission differed by both rate (infused at a

    standard rate of 128mL/min) and type (Hartmann’s

    solution) respectively from what is recommended in

    the guideline. Furthermore, 2 patients were

    prescribed sodium bicarbonate.

    Antibiotics were prescribed in 23 patients. 10

    patients had no documented source of infection, 5

    patients had documented respiratory tract infection,

    4 patients had a urinary tract infection, 2 patients

    had gastroenteritis while one patient had antibiotics

    started for pelvic inflammatory disease. White cell

    count on admission was found to be negatively

    correlated with initial HCO3- and eGFR (ρ=-0.630,

    P=

  • Editorial OrgOdRe

    Original Article

    Malta Medical School Gazette Volume 03 Issue 03 2019

    According to the JBDS guidelines one of the

    criteria defining DKA is a serum ketonaemia of ≥

    3.0mmol/L or significant ketonuria of ≥ 2+ on

    standard urine sticks.4 Locally ketone meters are not

    available yet and this may delay the detection of

    ketones in patients who are unable to provide a

    urine sample at A&E. Ketone meters detect β-

    hydroxybutyrate which is the main type of ketone

    produced in DKA as opposed to acetoacetate

    detected by the standard urine dipsticks. The latter

    also sometimes gives false positive results and the

    presence of acetoacetate in urine lags behind the

    actual systemic ketone production, therefore

    delaying both diagnosis and resolution of DKA.6

    Local guideline recommends use of a VRII and

    in 7 cases (18%), a further increase in insulin

    treatment recommended. Updates in JBDS

    guideline suggest using a fixed-rate insulin infusion

    (FRII) rather than VRII. FRII consists of

    prescribing a fixed insulin regime according to

    weight, thus partially accommodating for the very

    obese patients4 and enabling rapid ketone clearance.

    In 4 cases (10%) long-acting insulin (glargine) was

    continued together with intravenous short-acting

    insulin infusion. Continued use of background

    insulin avoids rebound hyperglycaemia when

    intravenous insulin is stopped and should also

    shorten duration of inpatient stay.7

    Initial intravenous fluid recommended in

    current guideline is 0.9% NaCl, which is to be

    changed to 5% dextrose in 0.9% NaCl if BGM <

    11mmol/L and to 10% dextrose if BGM

  • Editorial OrgOdRe

    Original Article

    Malta Medical School Gazette Volume 03 Issue 03 2019

    insulin infusion. The introduction of ketone meters

    to measure ketones in the blood would expedite

    DKA diagnosis, facilitate monitoring of the patient

    admitted with DKA and accurately identify

    resolution of DKA early while the administration of

    insulin infusion at a fixed rate, tailored to the

    individual patient according to the patient’s weight,

    would contribute to rapid ketone clearance thus

    improving the overall management of the patient

    admitted with DKA.

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